Metal salts of fatty acid derivatives of amino acids

ABSTRACT

The invention relates to new compositions useful in the field of treatment of man, animals and plants. The compounds are of the formula : ##STR1## wherein : R-CO is the acyl moiety of a straight fatty acid RCOOH comprising from 6 to 20 carbon atoms. ##STR2## represents either the skeleton of the amino acid ##STR3## in which R 1  is conventionally used to allow the generic designation of any of the naturally occurring α amino acids obtained by degradation of the various proteins, or the ensemble of skeletons of all the α aminoacids obtained by complete hydrolysis of the natural proteins, said compositions containing the alpha aminoacids in proportions similar to that ones existing in the proteins treated. 
     M is a metal selected from within: magnesium, calcium, iron, cobalt, manganese, copper, zinc, molybdenum and aluminium. 
     m is the valency of the selected M 
     n is an integer inferior to m. Some detailed examples of compositions are given.

This invention relates to new metallic compositions of matter presentingspecially an interest in the field of treatment of men, animals andplants.

It is well-known that discrete amounts of metals can be met in allliving organisms (human beings, animals, plants) and that theyconstitute, in all the cases, indispensable elements. The metals aregenerally encountered under the form of protidic complexes(metallo-proteins), glucido protidic or lipido protidic complexes.

These metallic structures play a specific role which varies with thenature of the metal and with the structures of the complexing moleculeitself; their action occurs in the field of biocatalysis or in themetabolic exchanges which allow the survival or the growing of theorgans or of the organisms.

The major problem lies in the appropriate selection of the complexingstructures which must be of such a nature as to allow an acceptableassimilation or absorption by the organ or the organism.

It is well-known that lipoaminoacids and lipopolyaminoacids can easilygo through the tissues and cellular membranes due to their specific lipoprotidic structures fully compatible with those tissues; althoughwater-insoluble, these lipoaminoacids and lipopolyaminoacids arenevertheless entitled of a certain ionisation capacity which comes fromthe carboxylic group in alpha position of the amino group; similarly thewater insoluble salts of the lipoaminoacids present the samecharacteristics while bringing together the selected metal.

Accordingly this invention provides the new composition of matter of theformula: ##STR4## wherein: R--CO is the acyl moiety of a straight fattyacid RCOOH comprising from 6 to 20 carbon atoms. ##STR5## representseither the skeleton of the amino acid ##STR6## in which R₁ isconventionally used to allow the generic designation of any of thenaturally occurring α amino acids obtained by degradation of the variousproteins, or the ensemble of skeletons of all the αaminoacids obtainedby complete hydrolysis of the natural proteins, said compositionscontaining the alpha aminoacids in proportions similar to that onesexisting in the proteins treated.

M is a metal selected from within: magnesium, calcium, iron, cobalt,manganese, copper, zinc, molybdenum and aluminium.

m is the valency of the selected M.

n is an integer inferior to m.

The metals retained hereinabove have been specially selected for theyare normal constituents of human, animal or vegetable tissues and nottoxic to these tissues. Molybdenum and zinc are to be used only inpreparations for the treatment of plants whereas all the others aresuitable for compositions for the treatment of human and animal tissues.

This invention provides for instance compositions to be used in humanand animal therapies for the correction of deficiencies in some of themetals above indicated (preferred forms of administration are creams,ointments and gelatin capsules for instance) and compositions to be usedin the treatment of plants which could be presented under the form ofaqueous emulsions.

Some examples of formulations are given below:

    ______________________________________                                        I.-  CREAMS FOR TOPICAL USE (proportions in weights)                          A/     Magnesium palmitoyl collagenate                                                                     5                                                       Polyethylene cetylic alcohol                                                                        5                                                       Glycerine             5                                                       Stearine              7                                                       Isopropylpalmitate    10                                                      Conservative agent    85                                                      water q.s.            100                                              B/     Magnesium caprylylglycinate                                                                         1                                                       Polyethylene cetylic alcohol                                                                        1                                                       Glycerine             1                                                       Stearine              3                                                       Isopropylpalmitate    10                                                      Conservative agent    q.s.                                                    Water q.s.            100                                              C/     Calcium palmitoyl collagenate                                                                       5                                                       Polyethylene cetylic alcohol                                                                        5                                                       Glycerine             5                                                       Stearine              7                                                       Isopropylpalmitate    10                                                      Conservative agent    q.s.                                                    Water q.s.            100                                              II.- PREPARATIONS FOR ORAL ADMINISTRATION                                     A/     Iron palmitoyl collagenate                                                                          0.250 g                                                 Lactose               0.050 g                                                 (for a gelatin capsule of 0.3 g)                                       B/     Manganese palmitoylglycinate                                                                        0.250 g                                                 Lactose               0.050 g                                                 (for a gelatin capsule of 0.3 g)                                       C/     Cobalt palmitoyl methionate                                                                         0.250 g                                                 Lactose               0.050 g                                                 (for a gelatin capsule of 0.3 g)                                       III.-                                                                              FOR USE IN AGRICULTURE (Proportions in weights)                          Copper caprylyl methionate                                                                             5                                                    Polyoxyethylene cetylic alcohol                                                                        10                                                   Water q.s.               100                                                  ______________________________________                                    

These metallic complexes may be prepared either by double decompositionbetween their soluble salts (alkaline metal salts) and the appropriatemetallic soluble salt or by neutralization of the free carboxy group bya base or a metal hydrate. This well-known reactions need no specificdescription and lead to water insoluble substances which, afterprecipitation, filtration, washing and drying, give products, thespecifications of which are reported in following tables where thecompounds are classified by the selected metals.

    ______________________________________                                        A-ALUMINIUM SALTS                                                             No. 1-Caprylylglycinate                                                       [CH.sub.3(CH.sub.2).sub.6CONHCH.sub.2COO].sub.2 AlOH                                                    Molecular                                                                     weight : 444                                        No. 2-Caprylylcollagenate                                                      ##STR7##                 M.W. : 307                                           ##STR8##                                                                     of the ensemble of the aminoacids obtained by the hydrolysis                  of collagene                                                                  No. 3-Caprylylcystinate                                                        ##STR9##                 M.W. : 534                                          No. 4-Caprylylmethionate                                                       ##STR10##                M.W. : 592                                          No. 5-Palmitoylmethionate                                                      ##STR11##                M.W. : 814                                          ______________________________________                                    

    ______________________________________                                        A = Theoritical percentage                                                                       M.P. = melting point in                                    B = Found percentage                                                                             Celsius degrees                                                          % of Nitrogen                                                                           on the lipo                                           Ref. % of Metal         aminoacid                                                                             on the salt                                   No.  A      B      M.P.   A    B    A    B    Aspect                          ______________________________________                                        1    6.1    6.5    240°                                                                          6.9  6.8  6.3  6.1  white                                                                         powder                          2    8.8    9.6    +300°                                                                         5.7  5.4  4.5  4.2  "                               3    6.2    7.1    +300°                                                                         5.7  5.4  5.2  4.8  "                               4    4.5    4.8    184°                                                                          5.1  4.7  4.6  4.3  "                               5    3.3    3.2    66°                                                                           3.6  3.2  3.4  3.1  "                               ______________________________________                                    

    ______________________________________                                        B-CALCIUM SALTS                                                               No. 6-Caprylylglycinate                                                       (CH.sub.3(CH.sub.2).sub.6CONHCH.sub.2COO).sub.2 Ca                                                      M.W. :  442                                         No. 7-Dipalmitoylhydroxyprolinate                                              ##STR12##                M.W. : 1250                                         No. 8-Palmitoylcollagenic                                                      ##STR13##                M.W. :  758                                         please refer to compound number 2 for the                                      ##STR14##                                                                    No. 9-Palmitoylcaseinic                                                        ##STR15##                M.W. :  816                                          ##STR16##                                                                    except that collagene is replaced by caseine                                  No. 10-Caprylylcollagenate                                                     ##STR17##                M.W. :  532                                         Same definition as in compound 8.                                             No. 11-Caprylylcystinate                                                       ##STR18##                M.W. :  530                                         No. 12-Lauroylcollagenate                                                      ##STR19##                M.W. :  644                                         Same definition as in compound 8.                                             ______________________________________                                    

    ______________________________________                                        A = Theoritical percentage                                                                       M.P. = melting point in                                    B = Found percentage                                                                             Celsius degrees                                                          % of Nitrogen                                                                           on the lipo                                           Ref.  % of metal        aminoacid                                                                             on the salt                                   No.   A      B      M.P.  A    B    A    B    Aspect                          ______________________________________                                        No. 6 9.1    8.4    250°                                                                         6.9  6.8  6.3  5.9  white                                                                         powder                          No. 7 3.2    3.6    155°                                                                         2.3  2.1  2.2  2.1  "                               No. 8 5.3    4.9    170°                                                                         3.9  3.6  3.7  3.5  "                               No. 9 4.9    3.8    145°                                                                         3.6  3.1  3.4  2.9  "                               No. 10                                                                              7.5    6.8    172°                                                                         5.7  5.4  5.2  4.9  "                               No. 11                                                                              7.5    8.4    +250°                                                                        5.7  5.4  5.2  4.7  "                               No. 12                                                                              6.2    5.4    105°                                                                         4.6  4.3  4.3  4.1  "                               ______________________________________                                    

    ______________________________________                                        C-COBALT SALTS                                                                No. 13-Palmitoylcollagenate                                                    ##STR20##                M.W. : 777                                          same definition as in example 2                                               No. 14-Palmitoylmethionate                                                                              M.W. : 833                                           ##STR21##                                                                    No. 15-Caprylylcystinate  M.W. : 551                                           ##STR22##                                                                    No. 16 -Undecylenoylglycinate                                                 (CH.sub.2CH(CH.sub.2).sub.8CONHCH.sub.2COO).sub.2 Co                                                    M.W. : 539                                          No. 17-Lauroylglycinate                                                       (CH.sub.3(CH.sub.2).sub.6CONHCH.sub.2COO).sub.2 Co                                                      M.W. : 571                                          ______________________________________                                    

    ______________________________________                                        A = Theoritical percentage                                                                       M.P. = melting point in                                    B = Found percentage                                                                             Celsius degrees                                                          % of Nitrogen                                                                           on the lipo                                           Ref.  % of metal        aminoacid                                                                             on the salt                                   No.   A      B      M.P.  A    B    A    B    Aspect                          ______________________________________                                        No. 13                                                                              7.6    8.2    105°                                                                         3.9  3.6  3.6  3.2  violet                                                                        pink                                                                          powder                          No. 14                                                                              7.1    7.8    123°                                                                         3.6  3.2  3.3  3.1  "                               No. 15                                                                              10.7   11.5   240°                                                                         5.7  5.2  5.1  4.9  "                               No. 16                                                                              10.9   9.2    168°                                                                         5.8  5.4  5.2  4.7  "                               No. 17                                                                              10.3   9.3    145°                                                                         5.4  4.8  4.4  4.1  "                               ______________________________________                                    

    ______________________________________                                        D-COPPER SALTS                                                                No. 18-Caprylylglycinat                                                       (CH.sub.3(CH.sub.2).sub.6CONHCH.sub.2COO).sub.2 Cu                                                       M.W. : 463                                         No. 19-Caprylylmethionate                                                      ##STR23##                 M.W. : 611                                         No. 20-Palmitoylcollagenate                                                    ##STR24##                 M.W. : 781                                         please refer to compound number 2 for the                                      ##STR25##                                                                    No. 21-Palmitoylkeratinic                                                      ##STR26##                 M.W. : 821                                         Definition comparable to compound 20                                          except that collagene is replaced by keratine                                 No. 22-Caprylylcollagenate                                                     ##STR27##                 M.W. : 555                                         Same definition as in example 20                                              No. 23-Lauroylcollagenate                                                      ##STR28##                 M.W. : 669                                         Same definition as in example 20                                              No. 24-Oleyl collagenate of copper                                                                       M.W. : 829                                          ##STR29##                                                                    Same definition as in example 20                                              ______________________________________                                    

    ______________________________________                                        A = Theoritical percentage                                                                       M.P. : melting point in                                    B = Found percentage                                                                             Celsius degrees                                                          % of Nitrogen                                                                           on the lipo                                           Ref.  % of metal        aminoacid                                                                             on the salt                                   No.   A      B      M.P.  A    B    A    B    Aspect                          ______________________________________                                        No. 18                                                                              13.5   11.8   170°                                                                         6.9  6.7  6    5.7  green                                                                         powder                          No. 19                                                                              10.3   9.7    180°                                                                         5.1  4.7  4.6  4.3  "                               No. 20                                                                              8.1    7.3    85°                                                                          3.7  3.5  3.6  3.2  "                               No. 21                                                                              7.7    6.9    80°                                                                          3.7  3.4  3.4  3.1  "                               No. 22                                                                              11.4   9.8    145°                                                                         5.7  5.4  5.0  4.7  "                               No. 23                                                                              9.5    8.6    90°                                                                          4.6  4.3  4.2  3.8  "                               No. 24                                                                              7.6    6.9    55°                                                                          8.1  7.4  3.1  2.8  "                               ______________________________________                                    

    ______________________________________                                        E-IRON SALTS                                                                  No. 25-Palmitoylcollagenate                                                    ##STR30##                M.W. : 774                                          please refer to compound number 2 for the                                      ##STR31##                                                                    No. 26-Caprylylcollagenate                                                     ##STR32##                M.W. 550                                            same definition as in example 25                                              F-ZINC SALTS                                                                  No. 27-Caprylylglycinate                                                       ##STR33##                M.W.: 465                                           please refer to compound 2                                                    for the understanding of                                                       ##STR34##                                                                    G-MANGANESE SALTS                                                             No. 28-Palmitoylcollagenate                                                    ##STR35##                M.W. : 773                                          please refer to compound 2                                                    for the understanding of                                                       ##STR36##                                                                    No. 29-Caprylylglycinate                                                       ##STR37##                M.W. 455                                            Same definition as in example 28                                              ______________________________________                                    

    ______________________________________                                        A = Theoritical percentage                                                                       M.P. = melting point in                                    B = Found percentage                                                                             Celsius degrees                                                          % of Nitrogen                                                                           on the lipo                                                                           on the                                        Ref.  % of Metal        aminoacid                                                                             salt                                          No.   A      B      M.P.  A    B    A   B   Aspect                            ______________________________________                                        No. 25                                                                              7.23   6.46   90°                                                                          3.9  3.6  3.6 3.2 red ochre                                                                     powder                            No. 26                                                                              10.1   9.2    130°                                                                         5.7  5.4  5.1 4.6 "                                 No. 27                                                                              13.9   12.8   >200°                                                                        7.0  6.2  6.0 5.1 white powder                      No. 28                                                                              7.1    6.7    97°                                                                          3.9  3.6  3.6 3.2 beige powder                      No. 29                                                                              12     13.2   199°                                                                         6.9  6.8  6.1 5.8 "                                 ______________________________________                                    

    ______________________________________                                        H-MAGNESIUM SALTS                                                             No. 30-Palmitoylcollagenate                                                    ##STR38##                   M.W. : 742                                       please refer to compound number 2 for the                                      ##STR39##                                                                    No. 31-Caprylylcollagenate                                                     ##STR40##                   M.W. : 518                                       same definition as in example 30                                              No. 32-Palmitoylmethionate                                                     ##STR41##                   M.W. : 796                                       No. 33-Caprylylmethionate                                                      ##STR42##                   M.W. : 572                                       No. 34-Caprylylglycinate                                                      (CH.sub. 3(CH.sub.2).sub.6CONHCH.sub.2COO).sub.2 Mg                                                        M.W. :                                                                        424                                              No. 35-Lauroylaspartate                                                        ##STR43##                   M.W. : 337                                       No. 36-Caproylglycinate                                                       (CH.sub.3(CH.sub.2).sub.4CONHCH.sub.2COO).sub.2 Mg                                                         M.W. :                                                                        368                                              ______________________________________                                    

    ______________________________________                                        A = Theoritical percentage                                                                       M.P. = melting point in                                    B = Found percentage                                                                             Celsius degrees                                                          % of Nitrogen                                                                           on the lipo                                           ,Ref. % of Metal        aminoacid                                                                             on the salt                                   No.   A      B      M.P.  A    B    A    B    Aspect                          ______________________________________                                        No. 30                                                                              3.2    2.6    99°                                                                          3.9  3.6  3.8  3.4  White                                                                         powder                          No. 31                                                                              4.6    4.2    185°                                                                         5.7  5.4  5.4  4.8  "                               No. 32                                                                              3.0    2.7    157°                                                                         3.6  3.3  3.5  3.2  "                               No. 33                                                                              4.2    3.8    200°                                                                         5.1  4.7  4.9  4.7  "                               No. 34                                                                              5.6    5.2    185°                                                                         6.9  6.8  6.6  6.2  "                               No. 35                                                                              7.1    7.8    >200°                                                                        4.4  4.1  4.1  3.8  "                               No. 36                                                                              6.5    5.9    >200°                                                                        8.1  7.4  7.6  7.1  "                               ______________________________________                                    

The compositions according to this invention may be used, for instance:

for those containing calcium salts, for the treatment of affections inrelationship with the teeth and the bones;

for those containing aluminium salts in hygienic preparations actingagainst the sudation;

for those containing cobalt salts, as hemato poietic factors;

for those containing manganese and magnesium salts, as growing factorsmore particularly for cattle;

for those containing copper salts, as biosynthetic (synthesis ofcuproproteins) and in the treatment of cryptogamic diseases.

We claim:
 1. A compound of the formula ##STR44## wherein: (a) R--CO isthe acyl moiety of a straight fatty acid RCOOH comprising from 6 to 20carbon atoms;(b) ##STR45## represents the skeleton of the amino acid##STR46## in which R₁ is conventionally used to allow the genericdesignation of any of the naturally occurring amino acids obtained bydegradation of the various proteins; (c) M is a metal selected from thegroup consisting of magnesium, calcium, iron, cobalt, manganese, copper,zinc, molybdenum and aluminium; (d) m is the valency of the selected M;and (e) n is an integer inferior to m.
 2. A therapeutic composition forthe treatment of deficiencies in metal in living organisms, saidtherapeutic composition comprising a carrier and an effective amount ofan active ingredient which is at least one compound selected from thoseof claim 1.